Alpha-1-antitrypsin (also called alpha 1PI) is the major proteinase inhibitor in human sera. The most common form of this glycoprotein (i.e., the homozygote MM phenotype), as well as the homozygote ZZ phenotype which is associated with chronic obstructive lung diseases, have been purified using classical chromatographic procedures. Spectral studies will be used to study both native and chemically modified alpha 1PI from each of these variant forms. These studies include ANS-dye binding studies to probe for hydrophobic sites using fluorescence spectroscopy, and polarization fluorescence spectroscopy to study kinetic and thermodynamic interactions of alpha 1PI with various other proteins (enzymes, zymogens, etc.). In addition, in alpha 1PI deficiency states, the role of alpha 2-macroglobulin, another plasma proteinase inhibitor, assumes increased importance. Complexes of proteinases with alpha 2-macroglobulin retain a portion of their proteolytic activity. The scope and limitations of this activity are being investigated by a variety of techniques, including the use of fluorescence polarization measurements of fluorescein-labeled physiologically important peptides and proteins.